[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-376256-105":59,"doc-detail-376256-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","a-novel-cdk4-inhibitor-for-myeloid-protection-in-chemotherapy-treated-triple-negative-breast-cancer","A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer","","Despite progress in cancer therapy, chemotherapy often triggers dose-limiting haematologic toxicities that reduce treatment feasibility. This study evaluates AU2–94, a first-in-class selective CDK4 inhibitor, as a myeloid-protective strategy during myelosuppressive chemotherapy in triple-negative breast cancer (TNBC), including retinoblastoma (RB)-deficient settings. Using in vitro, ex vivo, and in vivo experiments, AU2–94 induces transient G1 arrest, prevents chemotherapy-driven DNA double-strand breaks, and limits apoptosis in bone marrow cells while preserving chemotherapy efficacy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-novel-cdk4-inhibitor-for-myeloid-protection-in-chemotherapy-treated-triple-negative-breast-cancer/376256/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-novel-cdk4-inhibitor-for-myeloid-protection-in-chemotherapy-treated-triple-negative-breast-cancer/376256.png","ImageObject",300,407,{"name":92,"@type":93},"Aran","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is AU2–94 and what protective role does it target?","Question",{"text":112,"@type":113},"AU2–94 is a first-in-class CDK4 inhibitor evaluated as a myeloid-protective agent. It aims to protect bone marrow cells from chemotherapy-induced damage in TNBC.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does AU2–94 reduce chemotherapy-related haematologic toxicity?",{"text":117,"@type":113},"AU2–94 induces a transient G1 arrest that prevents chemotherapy-induced DNA double-strand breaks, thereby reducing apoptosis in bone marrow cells. It also mitigates declines in red blood cells and neutrophils in relevant models.",{"name":119,"@type":110,"acceptedAnswer":120},"Does using AU2–94 affect the effectiveness of chemotherapy?",{"text":121,"@type":113},"In RB-deficient TNBC models, AU2–94 pretreatment before cisplatin reduced haematologic toxicity without compromising chemotherapy efficacy. The document frames AU2–94 as protective rather than interfering with treatment outcomes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},376256,1790636850,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},137455076865,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Investigational New Drugs (2025) 43:728–741  \n[https://doi.org/10.1007/s10637-025-01550-7](https://doi.org/10.1007/s10637-025-01550-7)  \nA novel CDK4 inhibitor for myeloid protection  \nin chemotherapy‑treated triple‑negative breast Cancer  \nAva Safaroghli‑azar1 · Laychiluh B Mekonnen1 · Ramin Hassankhani1 · Jimma Lenjisa1 · Sunita KC Basnet1 · Hajer Batayneh1 · Muhammed H Rahaman1 · Shudong Wang1  \nReceived: 10 April 2025 / Accepted: 22 May 2025 / Published online: 6 June 2025 © The Author(s) 2025  \nSummary  \nBackground Despite advances in cancer treatment, chemotherapy remains a cornerstone of clinical practice. However, its efficacy is often compromised by dose-limiting haematologic toxicities. Recent strategies aim to enhance chemotherapy tolerability while preserving its effectiveness. One emerging approach involves selective CDK4 inhibitors to serve as myeloidprotective agents in retinoblastoma (RB)-negative tumours, such as triple-negative breast cancer (TNBC) . Because bone marrow (BM) cells rely on RB for proliferation, CDK4 inhibitors may protect these cells while sparing RB-deficient tumour cells. The present study investigated the potential of AU2–94, a first-in-class CDK4 inhibitor, to protect BM cells during myelosuppressive chemotherapy in TNBC, beyond its established application in RB-positive cancers.  \nMethods This study employed in vitro, ex vivo, and in vivo experiments to evaluate the myeloid-protective effects of AU2–94 against chemotherapy-induced damage.  \nResults AU2–94 induced a transient G1 arrest that protects BM cells from chemotherapy-induced apoptosis by preventing DNA double-strand breaks. Pre-treatment with AU2–94 prior to 5-fluorouracil (5-FU) administration reduced BM cells apoptosis, preserved Ki67-positive cells, and mitigated declines in red blood cells and neutrophils. Similarly, AU2–94 pretreatment before cisplatin administration reduced cisplatin-induced haematologic toxicity in RB-deficient TNBC bearing mice without compromising the efficacy of chemotherapy.  \nConclusion These findings support the repurposing of AU2–94 as a myeloprotective agent, highlighting its therapeutic potential in RB-deficient tumours. With AU2–94 advancing to clinical trials, these results underscore its broader therapeutic promise, extending to both RB-positive and RB-negative cancer treatment.  \nGraphical abstract  \nSchematic representation of the proposed mechanism by which AU2–94 preserves bone marrow cells from cisplatin-induced toxicity in RB-deficient cancer. (A) DNA-damaging chemotherapeutic drugs like cisplatin induce tumour cell death and provoke double-strand DNA damage in rapidly proliferating cells, including bone marrow (BM) cells, leading to unwanted myelosuppression. (B) Pre-administration of the selective CDK4 inhibitor AU2–94 before cisplatin induces transient G1 arrest in BM cells, a phase critical for monitoring DNA integrity. This intervention prevents chemotherapy-induced double-strand DNA damage in BM cells, thereby aiding in myelopreservation. Given that TNBC-derived tumour cells often carry genetic  \n* Shudong Wang [shudong.wang@unisa.edu.au](shudong.wang@unisa.edu.au)  \n1 Drug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia  \nmutations in the retinoblastoma (RB) protein, these cells are resistant to CDK4 inhibition. Hence, the addition of AU2–94 to a cisplatin regimen does not interfere with treatment outcomes but solely functions as a myelopreservation strategy.  \nKeywords CDK4 inhibitor · Chemotherapy-induced myelosuppression · RB-negative tumour · Triple negative breast cancer  \nIntroduction  \nTriple-negative breast cancer (TNBC) presents a significant global health challenge due to its aggressive nature, early onset, high risk of metastasis, and limited treatment options [1]. Chemotherapy remains the cornerstone of TNBC treatment [2]; however, it frequently causes severe haematologic toxicities, necess","cbCaipuWcHLRtx7Z","https://ap.wps.com/l/cbCaipuWcHLRtx7Z","pdf",2211363,14,"English","# Summary\n## Background\n## Methods\n## Results\n## Conclusion\n# Keywords\n# Introduction","[{\"question\":\"What is AU2–94 and what protective role does it target?\",\"answer\":\"AU2–94 is a first-in-class CDK4 inhibitor evaluated as a myeloid-protective agent. It aims to protect bone marrow cells from chemotherapy-induced damage in TNBC.\"},{\"question\":\"How does AU2–94 reduce chemotherapy-related haematologic toxicity?\",\"answer\":\"AU2–94 induces a transient G1 arrest that prevents chemotherapy-induced DNA double-strand breaks, thereby reducing apoptosis in bone marrow cells. It also mitigates declines in red blood cells and neutrophils in relevant models.\"},{\"question\":\"Does using AU2–94 affect the effectiveness of chemotherapy?\",\"answer\":\"In RB-deficient TNBC models, AU2–94 pretreatment before cisplatin reduced haematologic toxicity without compromising chemotherapy efficacy. The document frames AU2–94 as protective rather than interfering with treatment outcomes.\"}]","A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer | PDF",1790217928,35]